Picornaviruses represent a very large virus family of small ribonucleic acid-containing viruses responsible for many serious human and animal diseases. Picornaviruses include four major groups: enteroviruses, rhinoviruses, cardioviruses and apthoviruses.
The human rhinoviruses consist of at least 100 serotypes and are the primary causative agents of the common cold. Because of the large number of serotypes, development of a vaccine is problematic; antiviral agents may therefore be the best approach to treatment. Rhinoviruses are composed of a surrounding capsid, which contains four viral proteins VP1, VP2, VP3 and VP4. Proteins VP1, VP2 and VP3 are organized into 60 repeating protameric icosahedral units. These are thought to be the cause of antigen diversity associated with these viruses.
Rhinovirus (HRV) infections lead to the common cold with symptoms such as fever, cough, and nasal congestion. HRV infection is the second most frequently recognized agent associated with pneumonia and bronchiolitis in infants and young children and commonly causes exacerbations of pre-existing airways disease in those with asthma, chronic obstructive pulmonary disease or cystic fibrosis. HRV infection is associated with one-third to one-half of asthma exacerbations depending on age and is linked to asthma hospitalizations in both adults and children.
Present treatment approaches include the application of rhinovirus specific RNA, as disclosed in the DE 19825395, which binds to the canyon region of the capsid, which is necessary to host receptor (e.g. ICAM-1, intercellular adhesion molecule-1) binding and cell infection.
Another method comprises the administration of soluble ICAM-1 proteins or derivatives of ICAM-1 as disclosed in the U.S. Pat. No. 6,326,004 and the U.S. Pat. No. 6,096,862 (tICAM-1, truncated ICAM-1) to neutralize viral particles (virions).
Chemical compounds with antiviral activity against rhinoviruses are disclosed in EP 0523803.
Rhinovirus symptoms are caused by an overly or unspecific reaction of the immune system. Therefore common treatment forms of a rhinovirus infection include administration of analgesics such as aspirin or acetaminophen/paracetamol, as well as localized versions targeting the throat (often delivered in lozenge form), nasal decongestants which reduce the inflammation in the nasal passages by constricting local blood vessels, cough suppressants (which work to suppress the cough reflex of the brain or by diluting the mucus in the lungs), and first-generation anti-histamines such as brompheniramine, chlorpheniramine, and clemastine (which reduce mucus gland secretion and thus combat blocked/runny noses but also may make the user drowsy).
Sulphated polysaccharides including carrageenans are known in the art for their antiviral efficacy. In a most interesting review, Gonzalez M. E. et al. (1987, Antimicrob. Agents Chemother. 31, 1388-1393) report an antiviral efficacy of different sulphated polysaccharides including iota-carrageenan against several animal viruses. Iota-carrageenan showed antiviral activity against the enveloped viruses HSV-1, HSV-2, Semliki Forest virus (SFV), vaccinia virus and African swine fever virus (ASF) and against the naked encephalomyocarditis (EMC) virus. Iota-carrageenan had no effect on the enveloped viruses vesicular stomatitis virus (VSV) and measles virus and on the naked viruses polio virus type 1 and adenovirus type 5.
US 2003/181415 A discloses antiviral activity of sulfated polysaccharides such as cellulose sulfate, against various enveloped viruses and in particular herpes simplex virus (HSV), Papilloma viruses and HIV.
WO 2005/004882 A discloses therapeutic treatment of viral infections, excluding rhinovirus infection, with sulphated polysaccharides such as carrageenans.
US 2005/171053 A1 discloses the use of lambda-carrageenan for inhibiting the spread of a sexually transmitted infection including HIV-1 infection.
Yamada et al. (1997, Carbohydrate Polymers, Appl. Scien. Publishers 32, 51-55) disclose an anti-HIV-1 activity of lambda-, kappa- and iota-carrageenan and their sulphated derivatives.
S. F. Tischer et al. (2006, Carbohydrate Polymers, Appl. Scien. Publishers 63, 459-465) disclose an activity of carrageenan isolated from Meristiella gelidium against herpes simplex and dengue virus.
Carlucci et al. (2004, Antiviral Research, Elsevier Science BV. 64, 137-141) disclose a protective effect of lambda-carrageenan on genital herpes simplex virus infection in mice.
Pujol et al. (2006, Planta Medica 72, 121-125) disclose an antiviral activity of a carrageenan isolated from Gigartina skottsbergii against intraperitoneal murine herpes simplex virus infection.
The term “carrageenan” is frequently used a collective term for linear sulphated galactose-based polysaccharides extracted from seaweed (rhodophyceae). It is mostly used as a thickener, gelling agent, stabilizer or emulsifier in pharmaceutical and food products. There exist more than 10 different carrageenans depending on the seaweed genus from which they are extracted. The three main types are iota-, kappa- and lambda-carrageenan, which differ slightly in their structure and degree of sulphatation. Iota-carrageenan is a soft-gel forming sulphated galactan predominantly extracted from red seaweed Gigartina stellata and Chondrus crispus. Kappa-carrageenan yields strong, rigid gels and is predominantly produced from Kappaphycus cottonii. Lambda-carrageenan, which is the most common form, is frequently used to thicken dairy products.
Despite the long known antiviral activity of some carrageenans against viruses such as, e.g. HIV or HSV, the mechanism of how carrageenans exhibit antiviral activity still needs clarification.
In the light of the above, the present invention now provides for a carrageenan-based antiviral composition suitable in the prophylactic or therapeutic treatment of rhinovirus infections (rhinitis).
Experiments leading to the present invention have surprisingly demonstrated that in spite of possible reservations in the art selected carrageenans exert antiviral activity against rhinovirus infections (rhinitis), with iota-carrageenan yielding the best results.